Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000471471 | SCV000550428 | uncertain significance | Familial cancer of breast | 2023-11-01 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 246 of the CHEK2 protein (p.Val246Leu). This variant is present in population databases (rs748504161, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 410000). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV001026337 | SCV001188698 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-05 | criteria provided, single submitter | clinical testing | The p.V246L variant (also known as c.736G>C), located in coding exon 5 of the CHEK2 gene, results from a G to C substitution at nucleotide position 736. The valine at codon 246 is replaced by leucine, an amino acid with highly similar properties. This alteration was seen in 1/732 breast cancer patients, 0/189 colorectal cancer patients and 0/490 cancer-free elderly controls in a Turkish population (Akcay IM et al. Int J Cancer, 2021 01;148:285-295). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |